Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior

• Material Type: 博士論文
• Title: Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior
• Author/Editor: Komori, Takashi; Okamura, Kazuya; Ikehara, Minobu; Yamamuro, Kazuhiko; Endo, Nozomi; Okumura, Kazuki; Yamauchi, Takahira; Ikawa, Daisuke; Ouji-Sageshima, Noriko; Toritsuka, Michihiro; Takada, Ryohei; Kayashima, Yoshinori; Ishida, Rio; Mori, Yuki; Kamikawa, Kohei; Noriyama, Yuki; Nishi, Yuki; Ito, Toshihiro; Saito, Yasuhiko; Nishi, Mayumi; Kishimoto, Toshifumi; Tanaka, Kenji F; Hiroi, Noboru; Makinodan, Manabu
• Author Heading: Komori, Takashi; Okamura, Kazuya; Ikehara, Minobu; Yamamuro, Kazuhiko; Endo, Nozomi; Okumura, Kazuki; Yamauchi, Takahira; Ikawa, Daisuke; Ouji-Sageshima, Noriko; Toritsuka, Michihiro; Takada, Ryohei; Kayashima, Yoshinori; Ishida, Rio; Mori, Yuki; Kamikawa, Kohei; Noriyama, Yuki; Nishi, Yuki; Ito, Toshihiro; Saito, Yasuhiko; Nishi, Mayumi; Kishimoto, Toshifumi; Tanaka, Kenji F; Hiroi, Noboru; Makinodan, Manabu
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2024-05
• Publication Date (W3CDTF): 2024-05
• Alternative Title: ミクログリアが分泌する脳由来神経栄養因子は内側前頭皮質の神経発達と社会性行動を制御する
• Periodical title: Molecular psychiatry
• No. or year of volume/issue: 29 5
• Volume: 29
• Issue: 5
• Pages: 1338-1349
• ISSN (Periodical Title): ISSN : 1359-4184
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2024-06-26
• Dissertation Number: 乙第1533号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Molecular biology; Neuroscience
• Target Audience: 一般
• Note (General): type:Thesis; Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.; 権利情報：© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.; identifier:Molecular psychiatry. 2024 May, vol.29, no.5, p.1338-1349; identifier:1359-4184; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4392; identifier:Molecular psychiatry, 29(5): 1338-1349
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4392/1/01%e4%b9%991533%e6%9c%ac%e6%96%87.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4392/2/02%e4%b9%991533%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4392/3/03%e4%b9%991533%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1038/s41380-024-02413-y
• Periodical Title (NCID): AA11164978; https://ci.nii.ac.jp/ncid/AA11164978
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU